Combining Optimal Control Theory and Molecular Dynamics for Protein Folding

A new method to develop low-energy folding routes for proteins is presented. The novel aspect of the proposed approach is the synergistic use of optimal control theory with Molecular Dynamics (MD). In the first step of the method, optimal control theory is employed to compute the force field and the optimal folding trajectory for the atoms of a Coarse-Grained (CG) protein model. The solution of this CG optimization provides an harmonic approximation of the true potential energy surface around the native state. In the next step CG optimization guides the MD simulation by specifying the optimal target positions for the atoms. In turn, MD simulation provides an all-atom conformation whose positions match closely the reference target positions determined by CG optimization. This is accomplished by Targeted Molecular Dynamics (TMD) which uses a bias potential or harmonic restraint in addition to the usual MD potential. Folding is a dynamical process and as such residues make different contacts during the course of folding. Therefore CG optimization has to be reinitialized and repeated over time to accomodate these important changes. At each sampled folding time, the active contacts among the residues are recalculated based on the all-atom conformation obtained from MD. Using the new set of contacts, the CG potential is updated and the CG optimal trajectory for the atoms is recomputed. This is followed by MD. Implementation of this repetitive CG optimization - MD simulation cycle generates the folding trajectory. Simulations on a model protein Villin demonstrate the utility of the method. Since the method is founded on the general tools of optimal control theory and MD without any restrictions, it is widely applicable to other systems. It can be easily implemented with available MD software packages

Metabolomics Reveals Reduction of Metabolic Oxidation in Women with Polycystic Ovary Syndrome after Pioglitazone-Flutamide-Metformin Polytherapy

Polycystic ovary syndrome (PCOS) is a variable disorder characterized by a broad spectrum of anomalies, including hyperandrogenemia, insulin resistance, dyslipidemia, body adiposity, low-grade inflammation and increased cardiovascular disease risks. Recently, a new polytherapy consisting of low-dose flutamide, metformin and pioglitazone in combination with an estro-progestagen resulted in the regulation of endocrine clinical markers in young and non-obese PCOS women. However, the metabolic processes involved in this phenotypic amelioration remain unidentified. In this work, we used NMR and MS-based untargeted metabolomics to study serum samples of young non-obese PCOS women prior to and at the end of a 30 months polytherapy receiving low-dose flutamide, metformin and pioglitazone in combination with an estro-progestagen. Our results reveal that the treatment decreased the levels of oxidized LDL particles in serum, as well as downstream metabolic oxidation products of LDL particles such as 9- and 13-HODE, azelaic acid and glutaric acid. In contrast, the radiuses of small dense LDL and large HDL particles were substantially increased after the treatment. Clinical and endocrine-metabolic markers were also monitored, showing that the level of HDL cholesterol was increased after the treatment, whereas the level of androgens and the carotid intima-media thickness were reduced. Significantly, the abundance of azelaic acid and the carotid intima-media thickness resulted in a high degree of correlation. Altogether, our results reveal that this new polytherapy markedly reverts the oxidant status of untreated PCOS women, and potentially improves the pro-atherosclerosis condition in these patients

Optimization and control of offshore wind systems with energy storage

Wind energy is widely exploited as a promising renewable energy source worldwide. In this article, an optimization method for the control and operation of the offshore wind farm as an integrated system considering its operational, economic and environmental impacts is proposed. The state of the offshore wind farm development, and the challenges faced by the offshore wind farms, including the challenges of economic costs, operational reliability, and environmental impacts are reviewed and summarized. A systematic methodology is proposed to optimize the costs of an offshore wind farm system based on a framework that extends from the supervisory level dispatch strategies to individual pitch control for load reduction and fatigue mitigation. This holistic approach is able to improve the efficiency and economic performance of a wind farm through overall system optimization, while explicitly operating each wind turbine using a formally designed control framework leading to an extension of their service lifespan. This work provides thorough introduction and innovative solutions for many economic and environmental issues in offshore wind farm development and has strong application potential

The Impact of Education About Cervical Cancer and Human Papillomavirus on Women's Healthy Lifestyle Behaviors and Beliefs: Using the PRECEDE Educational Model

Background Early detection of cervical cancer improves the chances of successful treatment. Objective The aim of this study was to determine the effect of education about cervical cancer and human papillomavirus on the healthy lifestyle, behavior, and beliefs of Turkish women who were without cancer, using the PRECEDE education model. Methods This qualitative and quantitative study was conducted as a prospective, randomized, 2-group (intervention and control) trial at a community training center in north Turkey. A total of 156 Turkish women who were without cancer participated in this study. The semistructured interview form, the SF-36 Health Status Questionnaire, the Health Belief Model Scale for Cervical Cancer and Pap Smear Test, and the Healthy Lifestyle Behavior Scale II were used. Results The subdimension scores of the Health Belief Model Scale for Cervical Cancer and Pap Smear Test were found to be higher among women in the study group (cervical cancer seriousness, P =.001; health motivation, P =.001) as compared with the control group after the education program. The SF-36 Health Status Questionnaire domain scores for physical role limitations, mental role limitations, and general health perceptions increased in the study group after the intervention. Conclusion The posteducation health motivation of women in the study group was improved, the women's perceptions of obstacles to Papanicolaou testing decreased, and through increased knowledge and awareness, the rate of Papanicolaou testing increased. Implications for Practice Educational programs aimed at motivating women to increase their awareness of cervical cancer, preventing cervical cancer, and having Papanicolaou testing are necessary and beneficial in this sample. © 2019 Wolters Kluwer Health, Inc.Author Affiliations: Health Science Faculty, Department of Nursing (Dr Ko0); Medicine Faculty, Department of Obstetric Gynecology (Mrs Ozdez); Health Science Faculty, Department of Midwifery (Dr Topatan); and Health Services Vocational School (Mrs /NnarlN and Dr yener), Ondokuz MayNs University, Samsun; Ahmet Erdo?an Health Services Vocational School, B[lent Ecevit University, Zonguldak (Mrs DanacN); and Health Services Vocational School, G[m[zhane University (Mrs Palazo?lu), Turkey. This project, no. 214S560, was supported by TZBITAK